Effects of glucocorticoids on fetal and neonatal lung development.
Antenatal glucocorticoids have been used for 30 years to induce maturation of preterm fetal lungs. Stimulation of the pulmonary surfactant system has been regarded as the most important effect of antenatal glucocorticoids; however, as these drugs alter the expression of a large number of genes they affect the maturation of the lung in several other ways. Antioxidant enzyme production, lung fluid absorption and alveolar development are all affected by glucocorticoids administered in the perinatal period. There is evidence that glucocorticoids induce genes associated with the synthesis of surfactant proteins, fatty acid synthase, the epithelial sodium channel and the membrane protein sodium/potassium ATPase as well as several antioxidant enzymes including catalase, glutathione peroxidase and two superoxide dismutases. Glucocorticoids also increase the expression of vascular endothelial growth factor, which may inhibit alveolarization and lead to abnormally large alveoli. The use of both antenatal and postnatal glucocorticoids has increased in the past decade. However, as concerns about possible long-term effects have arisen, the mechanisms of how glucocorticoids alter the structure and function of the lungs needs to be determined to allow the development of more specific agents in the treatment of respiratory distress syndrome.